New methods of therapy for B cell leukemia will be evaluated using the murine BCL1 model of human prolymphocytic chronic lymphocytic leukemia (P-CLL). These will include cytoreductive therapy (splenectomy or total lymphoid irradiation) followed by immunotherapy with anti-idiotypic antibody coupled to ricin A chain or adoptive immunotherapy with allogeneic marrow. Evaluation of tumor growth will be performed using anti-idiotypic antibody in an indirect immunofluorescence assay to detect tumor cells in the lymphoid organs and blood of the treated mice. The goal stated above has been accomplished, i.e., mice have been "cured" of the BCL1 tumor using the combination of cytoreductive therapy and immunotoxin. Long-term follow-ups of these animals are in progress. We are now focusing our efforts on improving the therapeutic index of immunotoxins to (1)\reduce toxicity; (2)\increase potency so that they will successfully kill larger numbers of tumor cells and non-B cell tumors as well; and (3)\study the effects of anti-Ig immunotoxins on normal and neoplastic human B cells in vitro.